Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease

NCT ID: NCT00553631

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-29
• Study Completion Date: 2009-05-05

Brief Summary

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this non-inferiority study is to evaluate the efficacy and safety of GA-GCB (velaglucerase alfa) administered every other week in comparison to imiglucerase in treatment naive patients with type 1 Gaucher disease.

Detailed Description

Type 1 Gaucher disease, the most common form, accounts for more than 90% of all cases and does not involve the CNS. Typical manifestations of type 1 Gaucher disease include hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Gene-Activated® human glucocerebrosidase (GA-GCB; velaglucerase alfa) is produced in a continuous human cell line using proprietary gene-activation technology and has an identical amino acid sequence to the naturally occurring human enzyme. GA-GCB (velaglucerase alfa) contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This study was designed to determine the efficacy and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.

Conditions

Gaucher Disease, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GA-GCB

VPRIV™ ,velaglucerase alfa

Group Type: EXPERIMENTAL

velaglucerase alfa

Intervention Type: BIOLOGICAL

IV infusion, 60 U/kg every other week for 9 months

imiglucerase

Group Type: ACTIVE_COMPARATOR

imiglucerase

Intervention Type: BIOLOGICAL

IV infusion, 60 U/kg every other week for 9 months

Interventions

velaglucerase alfa

IV infusion, 60 U/kg every other week for 9 months

Intervention Type: BIOLOGICAL

imiglucerase

IV infusion, 60 U/kg every other week for 9 months

Intervention Type: BIOLOGICAL

Other Intervention Names

VPRIV™; gene-activated human glucocerebrosidase; Cerezyme®

Eligibility Criteria

Inclusion Criteria

Includes:

• The patient has a documented diagnosis and clinical manifestation of type 1 Gaucher disease
• The patient is at least 2 years of age.
• The patient has not received treatment for Gaucher disease (investigational products, miglustat, or imiglucerase) within 12 months prior to study entry, as documented in the patient's medical history.
• Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have negative results to a pregnancy test performed at the time of enrollment and as required throughout their participation in the study. Male patients must use a medically acceptable method of birth control throughout their participation in the study and must report their partner's pregnancy.
• The patient, the patient's parent(s) or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
• The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator.

Exclusion Criteria

Includes:

• The patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease.
• The patient has received treatment with any non-Gaucher disease-related investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted.
• The patient is known to be positive for human immunodeficiency virus (HIV).
• The patient is known to be positive for hepatitis B and/or C.
• The patient, patient's parent(s), or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
• The patient has a significant comorbidity(ies) that might affect study data or confound the study results (e.g., malignancies, primary biliary cirrhosis, autoimmune liver disease, etc.).
• The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Duke Children's Hospital & Health Center

Durham, North Carolina, United States

Your Health S.A.

Buenos Aires, , Argentina

Malabar Institute of Medical Sciences Ltd.

Calicut, Kerala, India

All India Institute of Medical Sciences

New Delhi, , India

KEM Hospital Research Centre

Pune, , India

Shaare Zedek Medical Center

Jerusalem, , Israel

Sociedad Espanola de Socorros Mutuos

Asunción, , Paraguay

National Research Center for Haematology

Moscow, , Russia

Hospital Universitario Miguel Servet

Zaragoza, , Spain

La Rabta Hospital

Tunis, , Tunisia

The Royal Free Hospital

London, , United Kingdom

Countries

United States; Argentina; India; Israel; Paraguay; Russia; Spain; Tunisia; United Kingdom

References

Zimran A, Elstein D, Gonzalez DE, Lukina EA, Qin Y, Dinh Q, Turkia HB. Treatment-naive Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials. Blood Cells Mol Dis. 2018 Feb;68:153-159. doi: 10.1016/j.bcmd.2016.10.007. Epub 2016 Oct 21.

Reference Type: DERIVED

PMID: 27839979 (View on PubMed)

Other Identifiers

2007-002840-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HGT-GCB-039

Identifier Type: -

Identifier Source: org_study_id